Diabetes, particularly non-insulin dependent diabetes mellitus (NIDDM), and its complications have become an increasingly important health problem for many American Indian populations. Data on the progression of NIDDM risk factors from early ages are scarce. This application proposes an epidemiologic study to evaluate a number of potential risk factors for NIDDM among members of the Cherokee Nation of Oklahoma. A stratified sample of subjects will be taken across a wide range of ages and degrees of Indian blood from childhood to adulthood. Some of these risk factors are also related to cardiovascular disease, a major complication of diabetes. The study will use a pseudo-cohort design to evaluate fasting glucose and insulin, glucose tolerance, and a number of potential risk factors for NIDDM (and cardiovascular disease), such as family history of diabetes, degree of Indian blood, obesity, diet, lipids and lipoproteins, physical activity, and social and economic factors, in the Cherokees aged 5 to 40 years. The major objectives are (1) to estimate the prevalence of obesity, impaired glucose tolerance (IGT), and diabetes in Cherokees less than 40 years of age, (2) to estimate the progressive differences in these variables from childhood to adulthood, (3) to determine the relationships between the risk factors and fasting glucose and insulin, and glucose tolerance at different ages and whether the relationships vary with age, (4) to estimate the age ranges in which obesity, elevated fasting glucose, glucose intolerance, insulin resistance, and abnormal lipids and lipoproteins occur, (5) to determine the effect of degree of Indian blood on fasting glucose, insulin, glucose intolerance, and other potential risk factors for NIDDM (and CVD), and (6) based on the information obtained, to recommend educational programs and other timely preventive measures and, consequently, reduce the burden of diabetes and improve the health status of American Indians. A pilot study of 218 participants was completed in 1992 with a planning grant from NIDDK. Through the pilot study, logistics of blood sample collection, transport, assay, and data collection and analysis have been worked out. Estimates of risk factors determined from the results of the pilot study facilitated sample size determination. The Cherokee Nation is selected as the study population because of its high prevalence of diabetes, varying degree of Indian blood, large membership, excellent health care facilities, and strong interest in research among the leaders and health professionals.